Sjogren's syndrome (SS) is a chronic, progressive autoimmune disorder characterized by lymphocytic infiltration of the salivary and lacrimal glands with a heterogeneous constellation of extra glandular manifestations. SS may occur as the primary disease, or secondary to another connective tissue disease such as rheumatoid arthritis or systemic lupus erythematosus. The molecular events that lead to SS are poorly understood but thought to involve multiple components of immune dysregulation. Our overall goal is to define important biological pathways that are dysregulated in SS patients using microarray technologies to examine genomic-scale gene expression profiles. We have recently established that differential gene expression patterns can be identified using peripheral blood mononuclear cells and initial analyses to date suggest that dysregulation of interferon-inducible genes may be important in SS. Here, we propose to define gene expression signatures in a large cohort of weft characterized SS patients, evaluate potential correlations between gene expression signatures and various phenotypic components of disease, and examine the durability and relationship with disease manifestations of the gene expression signatures over time. We will also collect essential biological samples that will allow a variety of confirmatory studies to be conducted using complementary methods. Characterization of gene expression profiles in SS has a high likelihood of conferring novel and important insights in the pathophysiologic mechanisms of this disease, and providing an important source of potential targets for development of novel diagnostic and therapeutic approaches.